S-adenosyl-L-methionine is the unexpected methyl donor for the methylation of mercury by the membrane-associated HgcAB complex

Mercury (Hg) is a heavy metal that exhibits high biological toxicity. Monomethylmercury and dimethylmercury are neurotoxins and a significant environmental concern as they bioaccumulate and biomagnify within the aquatic food web. Microbial Hg methylation involves two proteins, HgcA and HgcB. Here, we show that HgcA and HgcB can be heterologously coexpressed, and the HgcAB complex can be purified. We demonstrated that HgcA is a membrane-associated cobalamin-dependent methyltransferase and HgcB is a ferredoxin-like protein containing two [4Fe-4S] clusters. Further, spectroscopic and kinetic results demonstrate that S-adenosyl-L-methionine (SAM) donates the methyl group to Hg in a two-step reaction involving a methylcob(III)alamin intermediate including Co-thiolate ligation from a conserved Cys residue. Our findings uncover a biological role for SAM in microbial Hg methylation.

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Publication Details

Journal
Proceedings of the National Academy of Sciences
Published
2024-11-15
DOI
https://doi.org/10.1073/pnas.2408086121
Citations
7
Primary Topic
Mercury impact and mitigation studies
Type
article
Field-Weighted Citation Impact
2.20

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article

S-adenosyl-L-methionine is the unexpected methyl donor for the methylation of mercury by the membrane-associated HgcAB complex

Macon J. Abernathy, Alexander Johs, Katherine W. Rush, Jerry M. Parks et al.
7 citations
Proceedings of the National Academy of Sciences
Mercury impact and mitigation studies
2.20
article

S-adenosyl-L-methionine is the unexpected methyl donor for the methylation of mercury by the membrane-associated HgcAB complex

Macon J. Abernathy, Alexander Johs, Katherine W. Rush, Jerry M. Parks, Swapneeta S. Date, Angela S. Fleischhacker, Stephen W. Ragsdale, Ritimukta Sarangi, Kaiyuan Zheng
article en
7 citations

Abstract

Mercury (Hg) is a heavy metal that exhibits high biological toxicity. Monomethylmercury and dimethylmercury are neurotoxins and a significant environmental concern as they bioaccumulate and biomagnify within the aquatic food web. Microbial Hg methylation involves two proteins, HgcA and HgcB. Here, we show that HgcA and HgcB can be heterologously coexpressed, and the HgcAB complex can be purified. We demonstrated that HgcA is a membrane-associated cobalamin-dependent methyltransferase and HgcB is a ferredoxin-like protein containing two [4Fe-4S] clusters. Further, spectroscopic and kinetic results demonstrate that S-adenosyl-L-methionine (SAM) donates the methyl group to Hg in a two-step reaction involving a methylcob(III)alamin intermediate including Co-thiolate ligation from a conserved Cys residue. Our findings uncover a biological role for SAM in microbial Hg methylation.

Proceedings of the National Academy of SciencesVol. 121(47)
Oak Ridge National Laboratory (US), University of Michigan (US), SLAC National Accelerator Laboratory (US), Stanford Synchrotron Radiation Lightsource (US)
U.S. Department of Energy, National Institutes of Health, Office of Science, National Institute of General Medical Sciences, Basic Energy Sciences, Biological and Environmental Research, Chemical Sciences, Geosciences, and Biosciences Division, Oak Ridge National Laboratory, Brookhaven National Laboratory, SLAC National Accelerator Laboratory
Openalex Percentile: Top 13%
Mercury impact and mitigation studies
2.20
DOIOpen Access PDFOpenAlex
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